Mechanism of KLF9 in airway inflammation in chronic obstructive pulmonary
Abstract Background Chronic obstructive pulmonary disease (COPD) is an airway‐associated lung disorder, resulting in airway inflammation. This article aimed to explore the role of the krüppel‐like factor 9 (KLF9)/microRNA (miR)‐494‐3p/phosphatase and tensin homolog (PTEN) axis in airway inflammation...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-10-01
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| Series: | Immunity, Inflammation and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/iid3.1043 |
| _version_ | 1827775693962870784 |
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| author | Peijie Gu Zhen Wang Xin Yu Nan Wu Liang Wu Yihang Li Xiaodong Hu |
| author_facet | Peijie Gu Zhen Wang Xin Yu Nan Wu Liang Wu Yihang Li Xiaodong Hu |
| author_sort | Peijie Gu |
| collection | DOAJ |
| description | Abstract Background Chronic obstructive pulmonary disease (COPD) is an airway‐associated lung disorder, resulting in airway inflammation. This article aimed to explore the role of the krüppel‐like factor 9 (KLF9)/microRNA (miR)‐494‐3p/phosphatase and tensin homolog (PTEN) axis in airway inflammation and pave a theoretical foundation for the treatment of COPD. Methods The COPD mouse model was established by exposure to cigarette smoke, followed by measurements of total cells, neutrophils, macrophages, and hematoxylin and eosin staining. The COPD cell model was established on human lung epithelial cells BEAS‐2B using cigarette smoke extract. Cell viability was assessed by cell counting kit‐8 assay. miR‐494‐3p, KLF9, PTEN, and NLR family, pyrin domain containing 3 (NLRP3) levels in tissues and cells were measured by quantitative real‐time polymerase chain reaction or Western blot assay. Inflammatory factors (TNF‐α/IL‐6/IL‐8/IFN‐γ) were measured by enzyme‐linked immunosorbent assay. Interactions among KLF9, miR‐494‐3p, and PTEN 3′UTR were verified by chromatin immunoprecipitation and dual‐luciferase assays. Results KLF9 was upregulated in lung tissues of COPD mice. Inhibition of KLF9 alleviated airway inflammation, reduced intrapulmonary inflammatory cell infiltration, and repressed NLRP3 expression. KLF9 bound to the miR‐494‐3p promoter and increased miR‐494‐3p expression, and miR‐494‐3p negatively regulated PTEN expression. miR‐494‐3p overexpression or Nigericin treatment reversed KLF9 knockdown‐driven repression of NLRP3 inflammasome and inflammation. Conclusion KLF9 bound to the miR‐494‐3p promoter and repressed PTEN expression, thereby facilitating NLRP3 inflammasome‐mediated inflammation. |
| first_indexed | 2024-03-11T13:53:45Z |
| format | Article |
| id | doaj.art-ef51c54693e147aebeffb55262c5a4b4 |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-03-11T13:53:45Z |
| publishDate | 2023-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-ef51c54693e147aebeffb55262c5a4b42023-11-02T07:56:19ZengWileyImmunity, Inflammation and Disease2050-45272023-10-011110n/an/a10.1002/iid3.1043Mechanism of KLF9 in airway inflammation in chronic obstructive pulmonaryPeijie Gu0Zhen Wang1Xin Yu2Nan Wu3Liang Wu4Yihang Li5Xiaodong Hu6Department of Pulmonary and Critical Care Medicine Jiangyin Hospital of Traditional Chinese Medicine Jiangyin City ChinaDepartment of Pulmonary and Critical Care Medicine Jiangyin Hospital of Traditional Chinese Medicine Jiangyin City ChinaDepartment of Pulmonary and Critical Care Medicine Jiangyin Hospital of Traditional Chinese Medicine Jiangyin City ChinaDepartment of Pulmonary and Critical Care Medicine Jiangyin Hospital of Traditional Chinese Medicine Jiangyin City ChinaDepartment of Pulmonary and Critical Care Medicine Jiangyin Hospital of Traditional Chinese Medicine Jiangyin City ChinaDepartment of Pulmonary and Critical Care Medicine Jiangyin Hospital of Traditional Chinese Medicine Jiangyin City ChinaDepartment of Pulmonary and Critical Care Medicine Jiangyin Hospital of Traditional Chinese Medicine Jiangyin City ChinaAbstract Background Chronic obstructive pulmonary disease (COPD) is an airway‐associated lung disorder, resulting in airway inflammation. This article aimed to explore the role of the krüppel‐like factor 9 (KLF9)/microRNA (miR)‐494‐3p/phosphatase and tensin homolog (PTEN) axis in airway inflammation and pave a theoretical foundation for the treatment of COPD. Methods The COPD mouse model was established by exposure to cigarette smoke, followed by measurements of total cells, neutrophils, macrophages, and hematoxylin and eosin staining. The COPD cell model was established on human lung epithelial cells BEAS‐2B using cigarette smoke extract. Cell viability was assessed by cell counting kit‐8 assay. miR‐494‐3p, KLF9, PTEN, and NLR family, pyrin domain containing 3 (NLRP3) levels in tissues and cells were measured by quantitative real‐time polymerase chain reaction or Western blot assay. Inflammatory factors (TNF‐α/IL‐6/IL‐8/IFN‐γ) were measured by enzyme‐linked immunosorbent assay. Interactions among KLF9, miR‐494‐3p, and PTEN 3′UTR were verified by chromatin immunoprecipitation and dual‐luciferase assays. Results KLF9 was upregulated in lung tissues of COPD mice. Inhibition of KLF9 alleviated airway inflammation, reduced intrapulmonary inflammatory cell infiltration, and repressed NLRP3 expression. KLF9 bound to the miR‐494‐3p promoter and increased miR‐494‐3p expression, and miR‐494‐3p negatively regulated PTEN expression. miR‐494‐3p overexpression or Nigericin treatment reversed KLF9 knockdown‐driven repression of NLRP3 inflammasome and inflammation. Conclusion KLF9 bound to the miR‐494‐3p promoter and repressed PTEN expression, thereby facilitating NLRP3 inflammasome‐mediated inflammation.https://doi.org/10.1002/iid3.1043airway inflammationbronchoalveolar lavage fluidchronic obstructive pulmonary diseasecigarette smoke extractKLF9miR‐494‐3p |
| spellingShingle | Peijie Gu Zhen Wang Xin Yu Nan Wu Liang Wu Yihang Li Xiaodong Hu Mechanism of KLF9 in airway inflammation in chronic obstructive pulmonary Immunity, Inflammation and Disease airway inflammation bronchoalveolar lavage fluid chronic obstructive pulmonary disease cigarette smoke extract KLF9 miR‐494‐3p |
| title | Mechanism of KLF9 in airway inflammation in chronic obstructive pulmonary |
| title_full | Mechanism of KLF9 in airway inflammation in chronic obstructive pulmonary |
| title_fullStr | Mechanism of KLF9 in airway inflammation in chronic obstructive pulmonary |
| title_full_unstemmed | Mechanism of KLF9 in airway inflammation in chronic obstructive pulmonary |
| title_short | Mechanism of KLF9 in airway inflammation in chronic obstructive pulmonary |
| title_sort | mechanism of klf9 in airway inflammation in chronic obstructive pulmonary |
| topic | airway inflammation bronchoalveolar lavage fluid chronic obstructive pulmonary disease cigarette smoke extract KLF9 miR‐494‐3p |
| url | https://doi.org/10.1002/iid3.1043 |
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